학술논문
Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM
Document Type
article
Author
Heike Peterziel; Nora Jamaladdin; Dina ElHarouni; Xenia F. Gerloff; Sonja Herter; Petra Fiesel; Yannick Berker; Mirjam Blattner-Johnson; Kathrin Schramm; Barbara C. Jones; David Reuss; Laura Turunen; Aileen Friedenauer; Tim Holland-Letz; Martin Sill; Lena Weiser; Christopher Previti; Gnanaprakash Balasubramanian; Nicolas U. Gerber; Johannes Gojo; Caroline Hutter; Ingrid Øra; Olli Lohi; Antonis Kattamis; Bram de Wilde; Frank Westermann; Stephan Tippelt; Norbert Graf; Michaela Nathrath; Monika Sparber-Sauer; Astrid Sehested; Christof M. Kramm; Uta Dirksen; Olli Kallioniemi; Stefan M. Pfister; Cornelis M. van Tilburg; David T. W. Jones; Jani Saarela; Vilja Pietiäinen; Natalie Jäger; Matthias Schlesner; Annette Kopp-Schneider; Sina Oppermann; Till Milde; Olaf Witt; Ina Oehme
Source
npj Precision Oncology, Vol 6, Iss 1, Pp 1-17 (2022)
Subject
Language
English
ISSN
2397-768X
Abstract
Abstract The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.